Flucostat capsules 150mg, No. 1

• Cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including AIDS patients, organ transplantation ); the drug can be used to prevent cryptococcal infection in AIDS patients;

• generalized candidiasis, including candidemia, disseminated candidiasis, and other forms of invasive candidiasis (including infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be carried out in patients with malignant neoplasms, patients in intensive care units, patients receiving cytotoxic or immunosuppressive drugs, as well as in the presence of other factors predisposing to the development of candidiasis;

• candidiasis of the mucous membranes, incl. oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary infections, candiduria; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;

• genital candidiasis: treatment of vaginal candidiasis (acute and chronic recurrent), prophylactic use in order to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis;

• prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of cytotoxic chemotherapy or radiation therapy;

• mycoses of the skin, including mycoses of the feet, body, groin, pityriasis versicolor, onychomycosis and candidiasis of the skin;

• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.

The drug is taken orally.

For adults with cryptococcal meningitis and cryptococcal infections of other localization, 400 mg is prescribed on the first day, and then treatment is continued at a dose of 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination; for cryptococcal meningitis, therapy is usually continued for at least 6-8 weeks.

To prevent the recurrence of cryptococcal meningitis in AIDS patients, after completing the full course of primary treatment, fluconazole therapy at a dose of 200 mg / day can be continued for a long time.

With candidemia, disseminated candidiasis and other invasive candidal infections, the dose is on average 400 mg on the first day, and then 200 mg / day. With insufficient clinical efficacy, the dose can be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.

With oropharyngeal candidiasis, the drug is prescribed on average 50-100 mg 1 time / day; the duration of therapy is 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment may be longer.

In case of atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is prescribed in an average dose of 50 mg 1 time / day for 14 days in combination with local antiseptic agents for processing the prosthesis.

With other localizations of candidiasis (with the exception of genital candidiasis), for example, esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, the effective dose is on average 50-100 mg / day with a treatment duration of 14-30 days.

For the prevention of recurrence of oropharyngeal candidiasis in AIDS patients, after the completion of the full course of primary therapy, fluconazole can be prescribed 150 mg 1 time / week.

For vaginal candidiasis, fluconazole is taken once orally at a dose of 150 mg. To reduce the frequency of relapses of vaginal candidiasis, the drug can be used at a dose of 150 mg 1 time / month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.

For balanitis caused by Candida spp., Fluconazole is administered as a single oral dose of 150 mg.

For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. In the presence of a high risk of generalized infection, for example, in patients with expected severe or long-term neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed several days before the expected appearance of neutropenia; after an increase in the number of neutrophils more than 1000 / ?l, treatment is continued for another 7 days.

For mycoses of the skin, including mycoses of the feet, smooth skin, inguinal region and candidiasis of the skin, the recommended dose is 150 mg 1 time / week. or 50 mg once a day. The duration of therapy in normal cases is 2-4 weeks, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required.

With pityriasis versicolor, the recommended dose is 300 mg once a week. within 2 weeks; some patients require a third dose of 300 mg / week, while in some cases a single dose of 300-400 mg is sufficient. An alternative treatment regimen is the use of the drug at 50 mg 1 time / day for 2-4 weeks.

With onychomycosis, the recommended dose is 150 mg 1 time / week. Treatment should be continued until the infected nail is replaced (an uninfected nail grows out). For re-growth of nails on fingers and toes, it normally takes 3-6 months and 6-12 months, respectively.

With deep endemic mycoses, it may be necessary to use the drug at a dose of 200-400 mg / day for up to 2 years. The duration of therapy is determined individually and is 11-24 months for coccidioidomycosis, 2-17 months for paracoccidioidomycosis, 1-16 months for sporotrichosis, and 3-17 months for histoplasmosis.

In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose exceeding that in adults. Flucostat is used daily 1 time / day.

For candidiasis of the mucous membranes, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, a loading dose of 6 mg / kg may be prescribed in order to more rapidly achieve constant equilibrium concentrations.

For the treatment of generalized candidiasis and cryptococcal infection, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.

For the prevention of fungal infections in children with reduced immunity, in whom the risk of developing an infection is associated with neutropenia, which develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg / day, depending on the severity and duration of the persistence of induced neutropenia.

In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults) in accordance with the severity of renal failure.

In elderly patients in the absence of impaired renal function, the drug is used in accordance with the usual dosage regimen.

In patients with impaired renal function with a single dose, a change in the dose of the drug is not required. With repeated use of the drug with CC more than 50 ml / min, the drug is prescribed in an average dose. With CC from 11 to 50 ml / min, you should first prescribe a loading dose of 50 mg to 400 mg, then a dose of 50% of the recommended dose. Patients undergoing regular dialysis are given one dose of the drug after each hemodialysis session.

Active ingredient: fluconazole - 150 mg

Excipients: colloidal silicon dioxide (aerosil), corn starch, magnesium stearate, sodium lauryl sulfate, lactose.

The composition of the capsule shell: gelatin, methyl parahydroxybenzoate, propyl parahydroxybenzoate, titanium dioxide (E171), acetic acid.

• Simultaneous administration of drugs that prolong the QT interval (including terfenadine or astemizole);

• children under 3 years old;

• hypersensitivity to the drug or azole compounds similar in structure.

The drug should be used with caution in hepatic and / or renal failure, while taking potentially dangerous hepatotoxic drugs, with alcoholism, in the case of proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias).

Clinical and pharmacological group: Antifungal drug

Pharmaco-therapeutic group: Antifungal agent

pharmachologic effect

Antifungal drug. Fluconazole, a representative of the class of triazole antifungal agents, is a potent selective inhibitor of sterol synthesis in the fungal cell.

Active against pathogens of opportunistic mycoses, incl. caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp. The activity of fluconazole has also been shown in models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics

Suction

After oral administration, fluconazole is well absorbed. Bioavailability is 90%. Cmax of fluconazole in blood plasma after taking on an empty stomach at a dose of 150 mg is 90% of its content in plasma when administered intravenously at a dose of 2.5-3.5 mg / l.

Tmax is achieved within 0.5-1.5 hours after administration. Concomitant food intake does not affect oral absorption.

Plasma concentration is directly proportional to the dose taken.

Distribution

90% Css is achieved by 4-5 days of drug treatment (when taken 1 time / day).

The introduction of a loading dose (on the 1st day), 2 times higher than the average daily dose, allows you to reach 90% Css level by the 2nd day. The apparent Vd approaches the total body water content. Protein binding - 11-12%.

Fluconazole penetrates well into all body fluids. Concentrations of fluconazole in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, cerebrospinal fluid concentrations of fluconazole are about 80% of plasma levels.

In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are achieved, which exceed serum concentrations.

Withdrawal

T1 / 2 is about 30 hours.

Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is found unchanged in the urine. Fluconazole clearance is proportional to CC. Fluconazole metabolites were not detected in the blood.

Indications of the drug

• cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including AIDS patients, organ transplantation ); the drug can be used to prevent cryptococcal infection in AIDS patients;

• generalized candidiasis, including candidemia, disseminated candidiasis, and other forms of invasive candidiasis (including infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be carried out in patients with malignant neoplasms, patients in intensive care units, patients receiving cytotoxic or immunosuppressive drugs, as well as in the presence of other factors predisposing to the development of candidiasis;

• candidiasis of the mucous membranes, incl. oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary infections, candiduria; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;

• genital candidiasis: treatment of vaginal candidiasis (acute and chronic recurrent), prophylactic use in order to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis;

• prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of cytotoxic chemotherapy or radiation therapy;

• mycoses of the skin, including mycoses of the feet, body, groin, pityriasis versicolor, onychomycosis and candidiasis of the skin;

• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.

Side effect

From the digestive system: changes in taste, nausea, flatulence, vomiting, abdominal pain, diarrhea; rarely - liver dysfunction (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of ALT, AST, ALP).

From the side of the central nervous system: headache, dizziness; rarely - convulsions.

From the hematopoietic system: rarely - leukopenia, thrombocytopenia, agranulocytosis.

From the side of the cardiovascular system: an increase in the duration of the QT interval, flicker, ventricular flutter.

Allergic reactions: skin rash; rarely - malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.

From the side of metabolism: rarely - hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Others: rarely - renal dysfunction, alopecia.

Application during pregnancy and lactation

The use of Flucostat during pregnancy is possible only in the case of severe and potentially life-threatening fungal infections, when the expected benefit of treatment outweighs the possible risk to the fetus.

Since fluconazole is excreted in breast milk at concentrations close to plasma concentrations, it is not recommended to prescribe the drug during breastfeeding.

Application for violations of liver function

The drug should be used with caution in liver failure, simultaneously with the intake of potentially dangerous hepatotoxic drugs, in alcoholism.

If clinical signs of liver damage appear, which may be associated with fluconazole, the drug should be discontinued.

Application for impaired renal function

Patients with renal insufficiency (CC <50 ml / min) require correction of the dosage regimen.

Fluconazole is excreted mainly in the urine unchanged. With a single dose, a dose change is not required. In patients (including children and the elderly) with impaired renal function, with repeated administration of the drug, a loading dose of 50 mg to 400 mg should be initially administered.

When CC> 50 ml / min, the average recommended dose of the drug is used; with QC from 11 to 50 ml / min, a dose of 50% of the recommended one is used. For patients regularly undergoing hemodialysis, one dose of the drug is administered after each hemodialysis session.

Application in children

Contraindication: children under 3 years of age.

Use in elderly patients

In elderly patients in the absence of impaired renal function, the drug is used in accordance with the usual dosage regimen.

special instructions

In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, incl. with a lethal outcome, mainly in patients with serious concomitant diseases. There was no clear dependence of the incidence of hepatotoxic effects of fluconazole on the total daily dose, duration of therapy, gender and age of the patient. The hepatotoxic effect of fluconazole is usually reversible; its signs disappeared after discontinuation of therapy. If clinical signs of liver damage appear, which may be associated with fluconazole, the drug should be discontinued.

AIDS patients are more likely to develop severe skin reactions with many drugs. If a patient receiving treatment for a superficial fungal infection develops a rash that can be associated with taking fluconazole, the drug should be discontinued. If a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and fluconazole should be discontinued if bullous lesions or erythema multiforme appear.

Care must be taken when using fluconazole with cisapride, astemizole, rifabutin, tacrolimus or other drugs metabolized by cytochrome P450 isoenzymes.

Overdose

Symptoms: hallucinations, paranoid behavior.

Treatment: gastric lavage and symptomatic therapy are recommended. Since fluconazole is excreted in the urine, forced diuresis increases its excretion. Carrying out hemodialysis for 3 hours reduces the plasma concentration of fluconazole by about 50%.

Drug interactions

When using fluconazole with warfarin, an increase in prothrombin time was noted by 12%. In this regard, it is recommended to control the prothrombin time in patients receiving FlucostatЃ in combination with coumarin anticoagulants.

With the simultaneous use of fluconazole increases the T1 / 2 of oral hypoglycemic drugs - sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide). The joint appointment of fluconazole and oral hypoglycemic drugs is allowed, but the possibility of hypoglycemia should be taken into account.

The simultaneous use of fluconazole and phenytoin may be accompanied by an increase in the concentration of phenytoin in a clinically significant degree. Therefore, if the combined use of these drugs is necessary, it is necessary to monitor the concentration of phenytoin with a correction of its dose in order to ensure a therapeutic concentration in the blood plasma.

The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and a shortening of T1 / 2 of fluconazole from plasma by 20%. Therefore, in patients receiving rifampicin at the same time, it is recommended to increase the dose of fluconazole.

It is recommended to monitor the concentration of cyclosporine in the blood in patients receiving fluconazole, because when using fluconazole and cyclosporine in patients with a transplanted kidney, taking fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in the blood plasma.

Patients receiving high doses of theophylline, or who are likely to develop theophylline intoxication, should be monitored for early detection of symptoms of theophylline overdose. simultaneous administration of fluconazole leads to a decrease in the average rate of clearance of theophylline from plasma.

With the simultaneous use of fluconazole and terfenadine or cisapride, cases of adverse reactions from the heart have been described, including paroxysms of ventricular tachycardia (arrhythmias of the 'pirouette' type).

There are reports of the interaction of fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. Patients receiving rifabutin and fluconazole should be closely monitored.

With the simultaneous use of fluconazole and zidovudine, there is an increase in the concentration of zidovudine in plasma, which is caused by a decrease in the conversion of the latter into its metabolite.

With the simultaneous use of fluconazole with midazolam, the risk of psychomotor effects increases, with tacrolimus - the risk of nephrotoxicity increases.